1, 3, 5-triazinyl-(6)-aminophenylarsenic compound



Patented Nov. 16, 1943 (fi)-AMINOPHENYL.- ARSENIC COMPOUND f V, A. New York, N. Y., assignor' :to Parke, Davis: Company, Detroit, Mich, a

corporation of Michigan V filo-Drawing Original aipplication December 20,

1939, Serial'No,113 10,232. Divided andifliis' ap Mame menses, 1942,;-Seria1--No.. 453,646.

Iir-SwitgierlafidDecember 23, 1938 Y f z cl ms; omeg 242) This inventionrdatesto derivatives er tri azines containing' 'arsenic and has parliicellar; ;re= Iation to condensation productscontainihg1,3,5- triazine radicals and arsenic adid radi'calse Reference is made to rny coa'pending application Ser. No. 3103232, filed December 20,1939; of which this application is 'a division.

Condensation products of triazines with various amines are known and usedin the'manufacture of dyes. However, derivatives of. triazines containing arsenic have hithertonot been prepared.

It has now been found that highly active therapeutic derivatives of [1,3,5-triazinyl-(6) aminophenylf-arsonic' acids can be obtained by reacting. 1,3;5-tri'azih'e .cleii'vativ'e's. with pheasaarsonic acid derivatives. This. rear: "011 maybe efiected with halogen derivatives of trance "The resulting reacti n:proeuersgcamn necess'a be treated further by methodfs 'with. airlinenia or alkyl-amines. amino-halogen-derivatives :or' Lat-name are also suitable for carrying out the'pr'esent action of 2,4,s-tr1am'ine Laurence wi liha-logeno-phenyl-arsonic acids also givesv riseto the products emimedin this'i'n'vntion.

The new compounds, which are to be employed as medicinal preparations, have! proved to exert solution of a triazine derivative of the formula These compounds may be prepared lay-reacting with a substituted seem as er; we a; the Emma. a

V V "w-csinrigaiinsosng ily] one of W and Z being ahalogen radic'aiyand the other an amino radical. If desired, the reaction product may be treated with ammonia, alkyl amines, dialkyl amines, hydroxy-alkyl amines.

and dialkyl-aminoralkyl amines to react with any remainingtriazine halogen. atoms.

A few examples. illustrating the working or the present invention are given below, but the inven tion is not limited tothese specific cases.

' m di l,

parts} by weight of sodiuma amino phenyl arsonate 3.55 parts by weight off Wat r s dmpw s afine u n ion of an extraordinarily strong action-in experimental v trypanosomiasis in the mouse. The dose necesto ten times smaller sary for a lasting cure is up than in the case of the medicinal preparations derived from phehyl-arsonic acids hitherto used.

Thetoxicity is low; that-is, the-therapeutic: marin is considerable, which isparticularly impor r danger .ot poisoning attending tant in view of the the use of remedies containing arsenic.

The new compounds are 1,3,5e-triazine derivatives of the formula I e emraoarramm wherein X and, Yare each 5. radica l selected,

own" 7 'is'Yafwhite .powaer; about: eon

I "45 p p prance. i The. damp-fiend! in'sen bl in alcohol, :"ethergkienzene. The-solution in concentrated 18.5 parts by weight of cyanuric chIOride'QZ-Arfi trichlero-l.3,-triazine-) in 500 parts by weight .ofizwater inthe courseoi l [H0112 while pooling and stirring vigorously, After this time thepri- .rnary aromatic amine has disappeared; The

white reaction product Wln'err forms a; suspension is filtered off, washed with water andfthenwith acetone.

The resulting p-EZt-dichloro-1,3,5-triazinyl- (-6) l-aminophenyl-arsonic acid of the formula V or;

i -I can beldissolvecl in aqueous alkalis Without colsulphuric acid is colorless.

Example 2 a V The, moist p- [2,4-dichloro-1,3,5-triazinyl- (6) 1- laminophenyl-arsonic acid obtained in accord.-

ance with Example 1 is covered with 10 times the quantity of 10% ammonia and shaken at45 C. for 1 hour, whereby the product goes into com which plete solution. The excess ammonia is removed under reduced pressure. On acidification with hydrochloric acid p-[2-chloro-4-amino-1,3,5-triazinyl-(G l-aminophenyl-arsonic acid of the formula is isolated in the form ofsmallwhit'e crystals which are filtered' of! and washed with water and acetone.

The resulting compound is soluble in all alisand also on warming with an excess of dilute mineral acid. It is insoluble'in water, alcohol,'ether and 1 benzene. On heating to higher temperatures, thecompound decomposes melting point. i

7 without having a definite The moist p- [2,4-dichloro-1,3,5-triazinyl- (Si 1- aminophenyl-arsonic acid prepared in accordance with Example 1 ish'eated in an autoclave under pressure to 110-130" 'C. for about 2 hours with 10 times the quantity of 25% ammonia' When excess ammonia has been driven off, the

product istreated with excess hydrochloric acid,

whereupon the hydrochloride of p-EZA-diaminQ- 1;3,5-triazinyl-(6)l aminophenyl arsonic acid of the formula f v separates in smallwhite crystals. It is sucked oil? and washed with cold water. The compound is soluble in aqueous alkalis and separates in voluminous white'fiakes on the addition of acetic acid. The picrate forms bunches of fine small needles,'th'e chloro-platinat'e forms-small yellow crystals. 7 I

'Instead ofworking in an autoclave,'th'e reacv tion 0i. p [2,4 dichloro --1,3,5 triazinyl (6) aminophenyl-arsonic acid withammonia can also take place in an open ves's'el also-yielding p- [24- sonic acid.

H Example 4 H 36.5 parts'by weight of chloro '-'cyanuric-diamide (Liebigs Annalen, vol. 10, year'1834, page 43) kali s and" dilute mineral acids without coloration;

are'boiled for about 2 hours under reflux with a solution of 3l parts by weight ofatoxyl in 300 parts by weight ,ofwater whereupon the atoxyl disappears. The white reaction 1 product is brought into solution by the addition of ammonia.

The sulpl'iate of p-[2A-diamino lfij triazinylj (6)l-aminophenyl arsonic acidflis precipitated from theffilteied solution by sulphuric acid.f. The "arsenic acid corresponds in all its propertieswith the compound obtained-in accordance with Example 3.

i Z a-Process fo -4-amino-'1,3,5-tria'zinyl-' (6)] ammonia,

The same compounds can be prepared if triamino-triazine (melamine) is" reacted yvith halogeno-phenyl-arsonic acid '(German patent specifications 205,449, 250,264.

Mameli,':"Pattai Chemisches Zentralblatt year I, p'age 1091; year 1909, Ii, page 1856).

Example 5 I l0 partsiby weight of a 17% solution of methyl- V aminer'are poured over '1 part by weight of p-[2,4- dichloro-l ,3,5- triazinyl-(6)l aminophenyl ar sonic acid obtained in accordance with Example 1 1 whereby solution sets in with evolution of heat. The. solution is boiled-until the excessof methylne i fl iv ni ff-p fl e sn ih drb 'h o e is thenjadded, to render theproductjustacid to I ,p

congo paperupon which thelh r h dr t Pr,

[2,4-di methylamino -l,3,5-triazinylf (6) l-ain ino precipitates in small, whitegc ystalline needl s on cooling; I These needles are filtered ofi and Washed 'with'c'old water. The compound is soluble'inaLlitl is insoluble in ethera'nd benzene.

Instead of p-amino-phenylearsonic acid, its derivativesr or isomers, suchas; for instance, 4-oxy- 3-amino-(1) phenyl -'arsonic acid -(1) or 2-o'xy- 4-amino ph n za onic acid may bel mp y in all the e'xam ples given aboye, t v

I claim; 7 1 if f' w 1. p-l2-chloro-4 amino+1,3,5-triazinyl (651.. aminophenyl arsonic acid of the formula, I

sonic acid of the formu'la comprising reacting cyanuric chloride'with p- HaN-C aminophenyl-arsonic'acid and subsequent treat- 1 ment of the p-[2,4-dichloro-1,3,5 -triazinyl-(6)J- aminophenyl-arsonic acid with dilute aqueous l; ERN T A rthe preparationoi p-[2-chlorovam n he yl- 

